Phase I trial-qualitative mapping of barrett metaplasia: A prrequisite for intervention trials

Introduction: Barrett's metaplasia (BM) is associated with a 30-125 fold higher risk of esophageal adenocarcinoma than the general population. BM may present as a cellular mosaic with irregular tongues of intestinal epithelia, varying areas of dysplasia and other intermediate markers for cancer risk. These areas may be missed on routine biopsy. If such areas cannot be readily relocated, chemopreventive studies will remain unfeasible. Methods: Utilizing a specially adapted upper gastroscope (Pentax Precision Instruments) that is able to accurately evaluate distance from incisors and endoscopic rotation, chromoendoscopy with toluidine blue and systematic mapping (4 quadrant jumbo biopsies at 1 cm intervals) was performed twice on 13 patients with BM (second EGD 1-3 months after baseline study). All biopsy specimens were subjected to routine and immunohistochemical staining (PCNA, p53, Ki-67, bcl-2, erb-B2) as well as flow cytometry to create baseline and follow-up maps for each patient. Results: 26 EGDs performed/566 total biopsies, (mean/case 21.8,range 8-40). Procedure length averaged 41 min (23-94 min). There were no immediate or 30 day complications. Epithelia type was reproducibly identified with 94% accuracy on second endoscopic maps. Ploidy, p53, and Ki-67 status were also reproducibly identified on second endoscopic maps (98,90,86% respectively). Dysplasia was seen in 3/13 patients at similar sites each mapping. Aberrant Ki-67 staining was seen in reidentifiable sites predominately associated with dysplasia. bcl-2 and PCNA were relatively ubiquitous on biopsies, limiting their utility as markers. Conclusions: 1. Utilizing a specially modified gastroscope and this methodology, we have been able to reliably locate sites of dysplasia ands other biomarkers within a field of BM. 2. Patients had variable areas of dysplasia, cellular abnormalities, that may have been missed on standard endoscopic surveillance. 3. The ability to accurately access areas of BM should facilitate further chemopreventive efforts.